Method of preparing and using compositions extracted from vegetable matter for the treatment of neurological conditions

ABSTRACT

A composition is prepared by extracting and isolating phytochemical fractions from plant matter for treatment for neurological conditions and especially for migraine headaches, inflammations, dementia, and Alzheimer&#39;s Disease. The composition is enriched, preferably with two or more different fractions, namely: isoflavones, lignans, saponins and saponogenins, catechins, and phenolic acids. The two selected fractions are different from each other and are combined specifically to form a composition to treat a neurological condition. Soy is the preferred source of these phytochemicals; however, other plants may also be used, such as wheat, psyllium, rice, oats, red clover, kudzu, alfalfa, flax, and cocoa. The composition may be delivered in an easy to use or consume form, such as cream, pills, tablets, capsules, pellets, dry powder, health bars, food ingredients and supplements, soft gels, and the like.

This is a division of Ser. No. 09/616,205, filed Jul. 13, 2000 now U.S.Pat. No. 6,391,310, which, in turn, is a division of Ser. No.09/162,038, filed Sep. 28, 1998 (a formal application which replacedprovisional application Ser. No. 60/060,549 filed Oct. 2, 1997), nowU.S. Pat. No. 6,261,565, which, in turn, is a continuation-in-part ofSer. No. 09/035,588 filed Mar. 5, 1998, now U.S. Pat. No. 6,033,714,which, in turn, is a continuation-in-part of Ser. No. 08/868,629, filedJun. 4, 1997, now U.S. Pat. No. 5,792,503, which, in turn, is a divisionof Ser. No. 08/614,545, filed Mar. 13, 1996, now U.S. Pat. No.5,702,752.

This invention relates to compositions extracted from vegetable matterand more particularly to phytochemicals, including saponogenins andsaponins, catechins, lignans, phenolic acids, catechins and isoflavones,and especially those extracted from a family of plants including soy,flax, tea, and cocoa and methods of using these compositions asnutritional supplements or food additives.

BACKGROUND

Plant materials are known to contain a number of classes of organic lowmolecular weight compounds which exert bioactivity in various animals.Historically, these compounds have been considered to be somewhatnon-nutritive, however, recent scientific evidence now suggests thesecompounds may play an important role in the maintenance of health, inchemoprevention, and in the mitigation of certain conditions or diseasesassociated with the circulation of sex hormones, including sleepdisorders and vaginal dryness.

Edible plants normally contained in the diet, or materials used asherbal remedies/dietary supplements, may contain collections ofstructurally related compounds. These related substances are oftenunique in their amounts and distribution when compared among variousplant sources. The most notable groups of compounds exhibitingbioactivity are known as flavonoids, isoflavones, saponins, lignans,alkaloids, catechins and phenolic acids.

Epidemiology studies relating diet to disease suggest that dietarycomponents may predispose populations to reduced risk of certaindiseases. Far eastern populations consuming soy have reduced rates ofbreast, prostate and colon cancers and coronary heart disease, whilepopulations in Finland have reduced rates of prostate cancer.Researchers are just now studying the specific compounds in the diet tounderstand the basis for the epidemiological observations.

Among the various plants consumed in the diet, several are rich sourcesof phytochemicals. Soy products contain high amounts of isoflavones andsaponins. Unrefined diet grains include plants such as wheat, psyllium,rice, flax and oats that contain lignans. Cocoa contains catechins andphenolic acids. Certain non-dietary plants are also sources of the samechemical molecules, such as lignans and isoflavones in kudzu root or redclovers. Isoflavones and lignans act as weak estrogenic substances. Teaplants are also a rich source of phytochemicals, including catechins andphenolic acids.

Isoflavones can be used alone to treat or prevent breast cancer,prostate cancer, skin cancer, and colon cancer or as mechanisminhibitors. Isoflavones alone may also reduce or prevent varioussymptoms related to the onset and duration of menopause, including hotflashes and osteoporosis. Isoflavones alone may also be effective incertain cardiovascular applications, including heart disease, reducingcholesterol-lipid levels, modulating angiogenesis, and other vasculareffects. Moreover, isoflavones alone have been implicated in reducingheadaches, dementia, inflammation, and alcohol abuse, as well asimmunomodulation.

Lignans alone have been implicated in preventing or treating breastcancer, prostate cancer and colon cancer as well as reducing hotflashes, preventing osteoporosis and showing antiviral potential.Lignans also have antimitotic and fungicidal activity. A plant lignan,the catecholic nordihydro-guaiaretic acid, was a potent antioxidant onceused by the food industry.

Saponins alone have been implicated in preventing or treating skincancer, colon cancer, reducing serum cholesterol, and inimmunomodulation and antiviral activity. Saponins also exhibitantioxidant effects and act as free radical scavengers.

Phenolic acids have shown antioxidant activity.

People who eat a high soy diet show reduction of many of theseabove-discussed symptoms. This suggests that ingesting a combination ofthese phytochemicals in a ratio such as that found in soy may result inan additive or synergistic effect. However, a high soy diet has someundesirable effects, including flatulence, undesirable taste, andhesitancy among Western consumers to change their lifestyle toincorporate soy in their diets, even for such benefits.

Isoflavones, which are heterocyclic phenols, are understood to includethe soy compounds genistin, daidzin and glycitein, as well as biochaninA, equol, formnononetin, and o-desmethylangolensin and naturalderivatives thereof. These compounds and their aglycone or de-methylatedaglycone forms, such as genistein and daidzein, are believed to havesimilar activities once they are ingested. They are sometimes referredto as phytoestrogens.

Lignans are defined to be compounds possessing a 2,3-dibenzylbutanestructure. They include matairesinol, secoisolariciresinol,lariciresinol, isolariciresinol, nordihydroguaiaretic acid, pinoresinol,olivil, other compounds which may be precursors of enterolactone andenterodiol and modifications thereof, including diglucosides.

Phenolic acids include p-hydrobenzoic acid, protocatechuic acid, andvanillic acid. Other phenolic acids are chlorolenic acid, caffeic acid,feruiic acid, gallic acid, sinapic acid, syringic acid, coumaric acid,cinnamic acid, gentisic acid, salicylic acid, hydroxy benzoic acid andhydroxy phenyl acetic acids and derivatives. This list of phenolic acidsshould be understood to include the various isomers and derivativesfound in the natural vegetable source.

Catechins, or flavan-3-ols, include epigallocatechin, catechin,epicatechin and gallocatechin.

Saponogenins are C-27 sterols in which the side chain has undergonemetabolic changes to produce a spiroketal. Saponogenins occur naturallyas saponins, which are 3-O-glycosides of the parent steroid ortriterpenes. Digitonin from Digitalis is a saponin. Saponins includeglucosides of sapogenin such as triterpenoids or steroids andsaccharides such as glucose, arabinose, galactose or glucuronic acid.Typical examples of leguminous saponins are glycyrrhizin (glycyrrhetinicacid+glucuronic acid) contained in Glycyrrhiza glabra, soysaponincontained in soybean and alfalfasaponin contained in Medicago sativa.Saponins also include chemical entities identified as triterpene phenolssuch as tomatine, soyasapogenols A, B, C, D, E and F, ginsengosidefraction 3 and 4, medicagenic acid, hederagenin, glycyrrhizin digitonin,quillaja saponin, lucernic acid and zahnic acid. The naturalmodifications of these compounds found in the vegetable source are alsoincluded in this identification.

A need exists for an improved composition consisting substantially ofisoflavones, lignans, saponogenins, saponins, and/or phenolic acidswhich will produce improved results over any of these taken alone.Furthermore, a need exists for a composition in which the beneficialphytochemicals are enriched as compared to their original source. Thispermits individuals to conveniently consume such phytochemicals as anutritional supplement or as a food additive.

SUMMARY OF THE INVENTION

An object of this invention is to provide a convenient way forindividuals to consume isoflavones, lignans, saponins, catechins and/orphenolic acids, either as a nutritional supplement or as an ingredientin a more traditional type of food.

An other object of this invention is to provide an optimized extractcomposition of phytochemicals which is in sufficient concentration to bedelivered in an easy to consume dosasge such as a pill, tablet, capsule,liquid or ingredient in a food.

Yet another object of this invention is to prepare the phytochemicalextract to be delivered as a topical application in a cream or lotion.In this form, the isoflavones, lignans, saponins, catechins and/orphenolic acids are dispersed and suspended in a suitable liquid or gelmatrix to render a stable cream or lotion as the delivery vehicle.

A further object of this invention is to provide an extract concentratewhich is closely similar in chemical composition to the chemicalentities found in the natural plant source.

In keeping with this aspect of the invention, the isoflavones, lignans,saponins, catechins and/or phenolic acids are extracted from a suitablevegetable source to render a composition which is substantially moreconcentrated than the original material and by more than 5 times in oneor more of the desired bioactive components.

This extract may be used alone or combined with one or more other plantextracts to produce the optimized composition. Further, this extractcomposition may be formulated with one or more other dietary nutrients,such as vitamins, minerals, amino acids, etc., to provide a nutritionalsupplement further optimized for a desired health effect. All theseingredients may be combined with necessary binders, excipients,preservatives, colors and the like known to those in the industry inorder to produce a suitable tablet, capsule, pill, liquid, cream, powderor food ingredient.

These phytochemicals may be packaged and provided in final form by meansknown to the supplements and food ingredient industries. The materialsare intended to provide health and well-being benefits.

DETAILED DESCRIPTION OF THE INVENTION

The improved composition is obtained by fractionating a plant sourcehigh in isoflavones, lignans and other phytochemicals such as defattedsoybean flakes, soy molasses, soy whey, red clover, alfalfa, flax,cocoa, tea, or kudzu root. These may be fractionated along or incombination with these other plants known to be high in the variousisoflavones, lignans, saponins, catechins and phenolic acids. Thefractionation results in substantially removing water, carbohydrates,proteins, and lipids from the source material. The fractionation methodmay be preferably that disclosed in co-pending U.S. Pat. No. 5,702,752or U.S. Pat. No. 4,428,876, or an extraction using ethyl acetate orn-butanol may be used. U.S. Pat. No. 5,702,752 is assigned to theassignee of this invention.

Other extraction processes, which may be used alone or in combination,include differential solubility, distillation, solvent extraction,adsorptive means, differential molecular filtration and precipitation.

The preferred composition is an improvement over known commercialmaterials regarding the amount of phytochemicals per gram of substanceand the amounts of different phytochemicals present which affectphysiologic function.

These natural substances have been consumed in food sources for longperiods of time and more closely relate to the substances consumed whichprovide the basis for the epidemiological evidence for health benefits.Additional benefits may be derived from improved physical propertiesrelative to phytochemicals chemically modified from their original foodsource form.

The resulting composition is expected to comprise in a preferred form:between 5% and 95% isoflavones, between 0% and 70% lignans, and between2% and 70% saponins and sapogenins. In a more preferred form, thecomposition will be extracted from soy. In another preferred form, thecomposition will contain a ratio of (saponins plus saponogenins) toisoflavones from 1:100 to 100:1, with the isoflavones consistingpredominantly of naturally occurring derivatives of genistein and/or itsprecursor biochanin A and daidzein and/or its precursor formononetin,with a ratio of the genistein derivatives to daidzein derivatives from100:1 to 1:100. Preferably, the isoflavones are predominantlyglycosylated derivatives.

The composition's ratios may be readily varied by changing the plantsource or by combining several plant sources for extraction. Thus, asfurther study shows which phytochemical combinations are moreefficacious for certain health effects, the particular composition willalso vary.

It is known that isoflavones, lignans, and saponins can be usedadvantageously to treat or prevent various cancers, including breastcancer, prostate cancer, skin cancer, and colon cancer.

It is believed that the improved composition will provide increasedbenefits in the form of chemoprevention. Recent experiments appear toconfirm this belief.

EXAMPLE 1

An initial series of animal studies was made to investigate the effectsof dietary soy products on the growth of s.c. (SUBCUTANEOUS) implantedLNCaP in male SCID mice. A high isoflavone-containing soy proteinisolate (SPI) (2.0 mg isoflavones/g SPI) is provided by ProteinTechnology International (St. Louis. Mo.). A soy phytochemicals extract,soy phytochemicals concentrate (SPC) which contains 28.5% total soyisoflavones and a diverse amount of other soy phytochemicals, isprovided by Archer Daniels Midland Company (Decatur, Ill.). Thesematerials were used to prepare six experimental diets. Table 1 showsingredients of the diets.

Eight-week-old male SCID mice were s.c. injected on the right flank with2×10⁶ LNCaP cells from hosts, randomized into six groups (n=10) andassigned to one of the experimental diets. Food intake, body weight, andtumor volume were measured. At the termination of the experiment, bloodsamples were collected and serum separated for PSA analysis. An aliquotof tumor tissues was formalin-fixed, paraffin-embedded, and cut into 4μm sections for in situ histochemical detection of apoptotic cells, andimmunohistochemical analyses of angiogenesis and proliferation. Anotheraliquot was prepared for cell lysates for western blot to determine theexpression of apoptosis-related gene products.

Table 2 summaries the effects of treatment on food intake, body weight,isoflavone intake and tumor volume. Soy products did not significantlyalter food intake or body weight. Compared to casein-fed controls, tumorvolumes from mice treated with SPI (20%), SPC (1.0%), and SPI and SPC(1.0%) were reduced by 12%, 28% (P<0.04), or 40% (P<0.005),respectively. Factorial analysis indicated that there was no significanteffect of protein source on tumor growth. Linear regression analysisindicated that tumor volumes were inversely correlated to total dietaryisoflavones (Tumor volume (cm³)=−0008+2.121×Isoflavones (mg), R²=0.76,p<0.03).

Table 3 shows the effects of SPC at 1.0% of the diet on apoptosis,proliferation, and angiogenesis of tumors from a pilot study. Itindicates that dietary supplementation of soy phytochemicals inhibitsthe growth of LNCaP tumor in vivo by enhancing apoptosis and inhibitingproliferation of tumor cells. Its inhibitory effect on tumorangiogenesis is not significant which may be due to small sample size(n=2).

Results from in vitro study showed that genistein and soy phytochemicalconcentrate inhibited secretion of PSA by LNCaP cells into media. PSAconcentrations were reduced 68% and 74% by 25 and 50 μM of genisteintreatment respectively, and 31% and 42% by 25 and 50 μM of soyphytochemical concentrate treatment respectively.

TABLE 1 Ingredients of experimental diets (grams) Diet 1 Diet 2 Diet 3Diet 4 Diet 5 Diet 6 casein SPI Casein/LSPC SPI/LSPC Casein/HSPC SPI/HSPSPI 0 200 0 200 0 200 Casein 200 0 200 0 200 0 DL-methionine 3 3 3 3 3 3Corn starch 150 150 150 150 150 150 Sucrose 500 500 500 500 500 500Cellulose, BW200 50 50 50 50 50 50 Corn oil 50 50 50 50 50 50 MineralMix, S10001¹ 35 35 35 35 35 35 Vitamin Mix, V10001¹ 10 10 10 10 10 10Choline Bitartrate 2 2 2 2 2 2 Soy phytochemicals 0 0 2 2 10 10 Total(g) 1000 1000 1002 1002 1010 010 (isoflavones, mg/kg diet) 0 245 341 586705 950 ¹AIN formulation with minor modification by Dr E A Ulman,Research Diets, Inc

TABLE 2 n Final body weight, total food intake, total isoflavone intake,and tumor volume Food intake Total Tumor volume Treatment Body weightgrams/m isoflavone (cm³) Casein 22.4 ± 0.5¹ 46.6 ± 3.1  0.00 ± 0.00 2.32± 0.31² SPI 23.1 ± 0.7 46.2 ± 2.8 17.00 ± 6.37 2.06 ± 0.32 Casein/ 21.4± 0.7 41.2 ± 3.4 14.03 ± 14 1.88 ± 0.35 LSPC SPI/LSPC 22.6 ± 0.6 50.1 ±4.7 29.36 ± 2.76 1.66 ± 0.29* Casein/ 22.2 ± 0.7 44.8 ± 6.1 76.38 ±10.40 1.64 ± 0.22* HSPC SPI/HSPC 22.0 ± 0.6 47.5 ± 1.7 92.53 ± 3.22 1.39± 0.30** ¹Values are means ± SE. There are no significant differences offood intake or body weight among treatment groups. ²Compared withcontrol group, SPI/LSPC, casein/HSPC, and SPI/HSPC had significantlysmaller tumor volumes (*p < 0.04, **p < 0.005)

TABLE 3 Effects of treatment on apoptotic index (AI, % TUNEL),proliferation index (PI, % PCNA Staining) and angiogenesis (microvesseldensity) Microvessel Treatment AI (% TUNEL) PI (% PCNA) Density Control(n = 2)  6.07 ± 0.88 60.1 ± 1.1 12.5 ± 3.8 Casein/HSPC (n = 2) 10.75 ±0.54 51.7 ± 1.3  9.7 ± 0.7 P value <0.02 <0.01 >0.05 Values are means =SE.

In summary, preliminary results indicate that soy products inhibit thes.c. growth of LNCaP tumor in SCID mice, possibly via induction ofapoptosis, and inhibition of angiogenesis and proliferation.

Isoflavones or lignans can alleviate menopausal-related symptoms such ashot flashes and osteoporosis as well as alleviate symptoms associatedwith menstruation. This is further believed to be due to theirestrogenic activity. It is believed that the improved compositiondescribed here will alleviate these symptoms even more effectively.

Also, isoflavones positively affect various cardiovascular-relatedconditions, including heart disease, cholesterol (saponins alsopositively affect cholesterol), angiogenesis and other vascular effects.It is believed that the improved composition will produce results forthese cardiovascular conditions at least as beneficial as those hithertoknown and at a reduced cost.

As explained earlier, isoflavones, lignans, and saponins are known toindividually positively affect various neurological and immunologicalsymptoms. It is believed that the improved composition will result inalleviating neurological and immunological symptoms at least as well asthose compounds hitherto known and at a reduced cost. Moreover, it wouldbe expected that some synergism would arise out of the combinationdescribed herein.

The improved composition may be administered orally, parenterally, forinstance, subcutaneously, intravenously, intramuscularly,intraperitoneally, by intranasal instillation or by application of anaerosol spray to mucous membranes, or to the skin by an ointment or acream.

Administering the improved composition may be done with any suitablecarrier, in solid or liquid dosage form such as tablets, capsules,powders, soft gels, solutions, suspensions, emulsions, ointments, orcreams. The Improved composition may also be administered as a foodsupplement or as a food ingredient.

The amount of the improved composition administered will vary dependingon the person, the mode of administration, and the desired result. Aneffective amount is expected to be 10 mg to 2000 mg/per dose.

EXAMPLE 2

Tablet Manufacture

The composition provided for in this patent may be used to preparetablets or other dosage forms. An example of a capsule preparation isprovided in Example 2. The higher the concentration of the activecomponent, the easier it is to form a tablet or emulsion. This leads toan added ability to incorporate other dietary nutrients. An examplewould be to prepare a phytochemical tablet which incorporates calciumand vitamin E as a supplement to maintain bone health and/or reduce postmenopausal symptoms such as hot flashes. In an example of thisembodiment, a 600 mg dry compression tablet was prepared containing atotal of 125 mg of isoflavones concentrate (50 mg isoflavone compound).Included in the tablet formulation was a source of calcium andmagnesium.

Dry compression tablets were produced by first blending the followingingredients: 4 kg of the improved composition (39.83% isoflavones), 1.91kg sorbitol, 0.095 kg magnesium stearate, and 13.11 kg dicalciumphosphate in a 120 quart capacity Hobart mixer. This blend ofingredients was then dry compressed at 1 ton pressure with a Stokes BB2simple press into tablets having a total weight of 600 mg containing125.53 mg of the improved composition and therefore 50 mg of totalisoflavones.

Alternatively, a phytochemical concentrate may be provided in a singledosage form, a skin cream or as a food ingredient added to conventionalfood in amounts from 10 mg to 2000 mg/per dose, the purpose of which isto exert a positive effect on health and well being. These benefitsinclude: cancer prevention, estrogen and sex hormone related maladies,inhibition of the pituitary-thyroid-gonadotrophic axis, alcoholdependency reduction, modulation of the cardiovascular, immune andnervous systems, antiviral effects and analgesic effects.

EXAMPLE 3

Two-piece gelatin capsules were produced by filling the receiving end ofthe empty size “0” capsules with 0.106 g of the improved composition(44.35% isoflavones) and closed with the capping end, providing acapsule containing 47.2 mg of total isoflavones.

EXAMPLE 4

A comparison between various sources of phytochemical preparations isgiven in Table 4. It is readily seen that the phytochemical componentsof the composition of the “Isoflavone Concentrate” of this invention issubstantially higher than the corresponding amounts in the naturalvegetable materials. Notably, the amount of glycone isoflavones andsaponins are over 100 times more concentrated compared to the foodsource and over twenty times more concentrated compared to the germ ofthe plant which naturally concentrates these phytochemicals. Comparisonof the “Isoflavone Concentrate” of this invention to other concentratesshows that the isoflavone fraction predominates in these latterproducts, reducing the amount of other healthful phytochemicals.Additionally, the extraction methods of these other products employtechniques which modify the components, particularly the isoflavones, sothat they are not identical to the substances found in the naturalvegetable material (U.S. Pat. No. 5,637,562).

One version of the improved composition was compared to other previouslydescribed compositions. The results are shown in Table 4

TABLE 4 Comparative Products to the Invention Isoflavone IsoflavoneGlycosides in Aglycones in Genistein/ Phenolic Product Product ProductDaidzein Lignans Saponins Acids Example (mg/g) (mg/g) Ratio (mg/g)(mg/g) (mg/g) Improved 401.0  3.37  1.06 to 1 0.2 460.7 25.47composition Soybean  1.748-2.776^(a)  0.044^(a)-0.075  1.59-2.7 NA 0.9-3.2^(b) Soy Flour  1.969^(a)  0.045^(a)  358 0.0013  2.870^(c)(defatted Soy germ  24.32^(d)  0.85^(d) NA  16.7-1.98^(b) NA Product^(e)NA  2.5-6.5^(e)  0.5-3.5 NA NA NA patent (PTI) Product^(f) NA 5.1‥14.7^(f)  0.433-3.48 NA NA NA patent (PTI) Product^(g) NA 1.7-3.5^(g)  0.66-2.86 NA NA NA patent (PTI) PTI NA 970 12.8 NA NA NAproduct^(h) PTI NA 640  2.0 NA NA NA product^(h) Soy  27.6  0.1  1.37 NANA  5.788 Molasses (dried) Novogen^(l)  0.0 550  1-1.7 to 1 NA NA NA^(a)Wang H and Murphy P A, J Agric Food Chem 1994, 42, 1666-1673^(b)Anderson R L and Wolf W J, J Nutr 125 581S-588S, 1995 ^(c)Seo A andMorr C V, J Agric Food Chem 1984, 32, 530-533 ^(d)SoyLife^(™ promotional literature) ^(e)WO 95/10530, PCT/US94/10697 ^(f)WO95/10512, PCT/US94/10699 ^(g)WO 95/10529, PCT/US94/10696 ^(h)NCI paper^(l)Novogen promotional literature

EXAMPLE 5

The improved composition, containing the glycoside forms of isoflavones,has as one aspect an improved solubility at body temperature over thepreviously described compositions containing the aglycoside forms.

Separate solutions (0.02% in distilled water) were made for genistein,genistin, daidzein, daidzin, and isoflavone concentrate in volumetricflasks. Samples were then placed in a 37° C. water bath for 17 hours,followed by rapid filtration through a 0.2 micron syringe-type filter toremove particulates. Filtered samples were then analyzed for isoflavoneconcentration by HPLC. Results are tabulated as shown in Table 5.

TABLE 5 Differential Solubility of Isoflavone Glycosides vs. AglyconesIsoflavone Genistein Genistin Daidzein Daidzin sample (ppm) (ppm) (ppm)(ppm) Genistein 7.42 Genistin 33.89 Daidzein 3.64 Daidzin 48.51Isoflavone 0.492 30.075 0.672 37.69 Concentrate

The glycoside forms, genistin and daidzin, are at least 4.57 and 13.32fold higher in concentration at 37° C. than their corresponding aglyconeforms, respectively.

The modifications made to the isoflavones are to remove the carbohydrateattached to the isoflavone moiety. This modification renders theisoflavone less soluble in water. Maintenance of the naturalmodification, glycosylation, enhances solubility. This fact is shown inthe comparative solubility chart of Table 5. This chart shows that thegenistin isoflavone is 4.6 times higher and the daidzin isoflavone is13.3 times higher than the corresponding non-glycosylated form. Highersolubility can lead to better bioavailability to intestinal organisms.The glycosylation does not inhibit absorption in the gut because theintestinal microflora convert the glycone form to the aglycone formbefore absorption occurs.

EXAMPLE 6

Extraction of Lignans from Flax

Lignans can be readily extracted from flax using this following method.

978 g of defatted flax meal (F1) was extracted with 2000 g of 85%ethanol at 40° C. for 10 minutes, forming a slurry. The resulting slurrywas filtered and extraction was repeated twice with a total of 6000 g ofethanol.

The ethanolic fraction was then evaporated under vacuum at 70° C.,resulting in an aqueous fraction of 1186 g. The aqueous fraction wascombined with 1000 g of water and mixed.

The mixed sample was then ultra-filtered through a 5000 molecular weightcutoff membrane, resulting in a 767 g permeate fraction and a retentatefraction of 1283 g.

The retentate fraction was freeze-dried, resulting in a 27.84 g sample(F2).

The 767 g permeate fraction at 50° C. was fed to a 35 ml bed volume.XAD-4 resin column at a rate of 10 ml/min. The column effluent wascollected and dried, resulting in a 14.8 g sample (F3) XAD-4 is atrademark for an absorbent resin. available from Rohm & Haas.

The column was then eluted with four bed volumes (140 ml) of 70% ethanolat 50° C. The eluent sample was evaporated under vacuum at 70° C. anddried, resulting in a 1.79 g sample (F4). The four fractions were thenanalyze for their lignan content, measured as the concentration byweight of secoisolariciresinol. As Table 6 shows, this extraction methodenriches lignan concentration.

TABLE 6 LIGNAN CONCENTRATIONS AS SECOISOLARICIRESINOL FRACTION F1 F2 F3F4 SECO. CONC. (mg/g) 2.3 1.9 4.8 13.4 PHENOLIC ACID

While the present invention has been disclosed in terms of the preferredembodiment in order to facilitate a better understanding of theinvention, it should be appreciated that the invention can be embodiedin various ways without departing from the principles of the invention.Therefore, the invention should be understood to include all possibleembodiments, modifications and equivalents to the described embodimentwhich do not depart form the principles of the inventions as set out inthe appended claims.

What is claimed is:
 1. A method of treating a neurological conditionselected from the group consisting of migraine headaches, inflammations,dementia and Alzheimer's Disease comprising administering to a person anamount therapeutically effective in treating said neurological conditionof a composition comprising at least two fractions selected from thegroup consisting of isoflavones, lignans, saponins and saponogenins,catechins, and phenolic acids, said at least two phytochemical fractionsbeing different from each other.
 2. The method of claim 1 wherein saidphytochemical fractions are extracted from plant matter selected fromthe group consisting of soy, wheat, psyllium, rice, oats, red clover,kudzu, flax, alfalfa, tea, and cocoa.
 3. The method of claim 2 whereinsaid treatment is for Alzheimer's Disease.
 4. The method of claim 2wherein said treatment is for migraine headaches.
 5. The method of claim2 wherein said plant matter is selected from the group consisting of teaand flax.
 6. The method of claim 2 wherein said treatment is forinflammations.
 7. The method of claim 2 wherein said treatment is fordementia.
 8. The method of claim 2 wherein said therapeuticallyeffective amount is selected to inhibit thepituitary-thyroid-gonadotrophic axis.
 9. The method of claim 2 in whichsaid plant matter is soy.
 10. The method of claim 3 in which said soy isselected from the group consisting of soybean, soy foods, soy molasses,soy whey, soy protein, and soy flour.
 11. The method of claim 1 whereinsaid composition is formed into a product for oral delivery comprisingbetween about 10 milligrams and about 2000 milligrams of saidcomposition.
 12. The method of claim 1 wherein said composition isformed into a product for oral delivery selected from a group consistingof: a. a predetermined dosage of said composition; b. a gelatin capsule;c. a liquid; and d. a food supplement composition in a concentrated,easy to consume dosage.
 13. The method of claim 1 including the furtherstep of forming said composition into a product selected from a groupconsisting of a concentrate, dried powder, liquid, capsule, pellet,pill, a food supplement, health bar, intranasal, and spray.
 14. Themethod of claim 1 in which said composition is comprised of at least 70%by weight of said phytochemical fractions.
 15. The method of claim 1 inwhich at least one of the selected phytochemical fractions comprises atleast 10% by weight of said composition.
 16. The method of claim 1 inwhich said composition is comprised of at least 80% by weight of saidphytochemical fractions.
 17. The method of claim 1 in which saidcomposition is comprised of at least 90% by weight of said phytochemicalfractions.
 18. The method of claim 1 wherein said phytochemicalfractions are in the ranges of about 5%-95% isoflavones; 0%-70% lignans;2%-70% saponins and saponogenins.
 19. The method of claim 18 wherein theratio of saponins plus saponogenins to isoflavones in the composition isin the range of about 1:100 to about 100:1.
 20. The method of claim 1 inwhich the ratio of isoflavones to lignans in the composition is in therange of about 1000:1 to about 1:50.
 21. The method of claim 1 whereinsaid first phytochemical fraction is isoflavones and said secondphytochemical fraction is saponins and saponogenins.
 22. The method ofclaim 21 wherein said isoflavone fraction is selected from a groupconsisting of malonyl, acetyl, glucoside, and aglycone forms.
 23. Amethod for the treatment of neurological conditions comprising the stepsof: providing a composition made from plant matter in which saidcomposition is formed by selecting at least two phytochemical fractionsselected on a basis of effectiveness in treating a neurologicalcondition from the group consisting of isoflavones, lignans, saponinsand saponogenins, catechins, and phenolic acids, said at least twophytochemical fractions being different members of said group; andcombining said at least two phytochemical fractions; and administering atherapeutically effective amount of said composition to a person. 24.The method of claim 23 in which said neurological condition is selectedfrom the group consisting of migraine headaches, inflammations,dementia, and Alzheimer's Disease.
 25. The method of claim 23 in whichsaid plant matter is selected from one or more of the group consistingof soy, wheat, psyllium, rice, oats, red clover, kudzu, flax, alfalfa,tea, and cocoa.
 26. The method of claim 25 in which said plant matter issoy.
 27. The method of claim 26 in which said soy is selected from thegroup consisting of soybean, soy foods, soy molasses, soy whey, soyprotein, and soy flour.
 28. The method of claim 23 further comprising adietary supplemental nutrient selected from the group consisting ofvitamins and minerals.
 29. The method of claim 28 in which said dietarysupplemental nutrient is selected from the group consisting of dicalciumphosphate, magnesium stearate, calcium citrate, calcium malate, andother calcium sources.
 30. The method of claim 23 wherein saidcomposition is formed into a product for oral delivery selected from thegroup consisting of tablets, capsules, pills, concentrates, powders,liquids, and added food ingredients.
 31. The method of claim 30 whereinsaid product is a tablet comprising a. said composition; and b. a fillerselected from the group consisting of sorbitol, lactose, cellulose anddicalcium phosphate.
 32. The method of claim 31 wherein said tabletcomprises between about 15% and about 25% by weight of said compositionand between about 65% and about 85% by weight of said filler.
 33. Themethod of claim 31 wherein said tablet comprises a. between about 15%and about 25% by weight of said composition; b. between about 60% andabout 84% by weight of said filler; and c. between about 1% and about25% by weight of a dietary supplemental nutrient selected from the groupconsisting of vitamins and minerals.
 34. The method of claim 33 whereinsaid dietary supplemental nutrient is selected from the group consistingof dicalcium phosphate, magnesium stearate, calcium citrate, calciummalate, and other calcium sources.
 35. The method of claim 30 whereinsaid product for oral delivery is a capsule comprising: a. apredetermined dosage of said composition; and b. a gelatin capsule. 36.The method of claim 23 wherein said composition comprises between about10 milligrams and about 2000 milligrams of said phytochemical fractions.37. The method of claim 23 wherein said plant matter is fractionated tosubstantially isolate individual ones of said phytochemical fractions.